The effect of vitamin D supplementation on peripheral regulatory T cells and β cell function in healthy humans: a randomized controlled trial

Diabetes Metab Res Rev. 2011 Nov;27(8):942-5. doi: 10.1002/dmrr.1276.


Background: Increasing evidence supports the role of vitamin D (vitD) in modifying the risk to develop type 1 diabetes (T1D) and other autoimmune diseases. VitD3 might stimulate regulatory T cells (Tregs), a central player in the maintenance of self-tolerance. In addition, direct effects of vitD on β-cell function are postulated. The aim of our study was to evaluate the effect of a high dose vitD supplementation on Tregs frequency (%Tregs) and β-cell function assessed by a mixed meal tolerance test (MMTT) in healthy humans.

Methods: A double-blind, placebo controlled trial was performed in 59 healthy adult subjects (49% females). Subjects received oral vitD3 (140,000 IU monthly) or placebo for 3 months. %Tregs within 20,000 CD4+ T cells of peripheral blood was determined by multi-parametric FACS-analysis. A liquid MMTT was carried out before and after treatment.

Results: %Tregs increased significantly in the vitD group, but remained unchanged in the placebo group. Fasting C-peptide concentrations did not change significantly in either group. Similarly, the mean AUC for C-peptide after 3 months and the change in mean values from baseline to the end of the treatment were comparable in both groups.

Conclusions: A short time high dose vitD3 supplementation significantly increased the frequency of Tregs, but did not further improve β-cell function in apparently healthy subjects. The immunomodulatory potential of vitD might be an important mechanistic link for the association of vitD and T1D.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • C-Peptide / blood
  • Cholecalciferol / administration & dosage
  • Cholecalciferol / therapeutic use*
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Humans
  • Immunomodulation / drug effects
  • Immunomodulation / physiology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology*
  • T-Lymphocytes, Regulatory / drug effects*


  • C-Peptide
  • Cholecalciferol